Cap-Independent Translation

Whether or not an mRNA is translated is often thought to be a simple function of its steady-state concentration and the ab sence of inhibitory proteins or RNA structures in the 5' and 3' noncoding regions. The articles presented in this volume show an unexpected flexibility of the eukaryotic translational appara tus in the mechanism of translational initiation and provide new opportunities for regulation. Most or all mRNA molecules synthesized by RNA poly 7 merase II in eukaryotic cells contain a 5' terminal mGpppG dinucleotide, also known as the "cap structure. " RNAs carrying a cap structure have been shown to be more resistant to attack by exoribonucleases than their uncapped counterparts. Further more, the cap facilitates transport of the RNAs from the nucleus to the cytoplasm. In the cytoplasm, the cap functions as a binding site for the cap binding protein complex eIF-4, which enhances the translation of the RNAs by the eukaryotic trans lational apparatus. Specifically, it has been postulated that bind ing of e1F-4 to the 5' terminal cap facilitates the recruitment of ribosomal subunits onto the mRNAs via their free 5' ends (cap dependent translation). Accordingly, uncapped RNAs are generally translated more poorly than capped RNAs. However, during the past 6 years both viral and cellular mRNAs have been discovered that can be translated cap-independently.